ABSTRACT Support is requested for a Keystone Symposia conference entitled Skin Immune Crosstalk organized by Drs. Anna Di Nardo, Daniel H. Kaplan and Nathalie Boulanger. The conference will be held in Breckenridge, Colorado from February 15-18, 2021. Skin is a barrier environment where immune cells interact with the unique skin environment to maintain tissue homeostasis and induce immune responses. Skin immune cells can be recruited from the circulation, but many reside in the skin where they are strategically located at the barrier interface within a complex stromal matrix in proximity with commensal bacteria and the external environment. Recent discoveries have radically changed our knowledge of the skin immune system including the interplay between different skin-resident immune cell types and the realization that skin immune cells interact with non-immune compartments in the skin. Skin- resident immune cells are shaped by the cutaneous microbiome and interact with the peripheral nervous system. These complex interactions result in efficient host defense against many pathogens, but some bacteria, fungi, viruses and vector-borne pathogens have evolved mechanisms to evade these systems. This conference will bring together immunologists, skin biologists, and dermatologists to introduce all groups to these new discoveries, challenges, and therapeutic opportunities. We will provide the attendees with a clear understanding that the host skin is a complex environment designed to tolerate commensals and respond to pathogens. Joining with a concurrent vector-borne disease meeting will enable microbiologists and vector biologists to exchange knowledge with immunologists and skin biologists, allowing for consideration of how new discoveries regarding skin-immune cross talk can inform our understanding of vector-borne pathogen transmission.